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  • 1. Berglund, P
    et al.
    Stighall, M
    Jirström, K
    Rydén, L
    Ferno, M
    Nordenskjöld, Bo
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Oncology . Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Oncology UHL.
    Landberg, G
    Cyclin E confers a prognostic value in premenopausal breast cancer patients with tumours exhibiting an infiltrative growth pattern2008In: Journal of Clinical Pathology, ISSN 0021-9746, E-ISSN 1472-4146, Vol. 61, no 2, p. 184-191Article in journal (Refereed)
    Abstract [en]

    Aims: To investigate the prognostic value of cyclin E in relation to tumour growth pattern by analysing stage II primary breast cancers from premenopausal women not subjected to any further adjuvant treatment. To analyse the value of cyclin E as a predictor of tamoxifen response, by comparing untreated and treated patients with oestrogen receptor positive tumours. Methods: Breast cancer samples, assembled in tissue microarrays, were immunohistochemically stained for cyclin E and evaluated regarding the presence of nuclear staining. The overall growth characteristics of each tumour were assessed using whole tissue sections. Results: Tumours displaying a pushing margin phenotype were strongly associated with high cyclin E levels, lymph node negative disease, a high histological grade and oestrogen receptor negativity, and exhibited a better prognosis compared to tumours with an infiltrative growth pattern. In the total cohort of non-treated patients (n = 187), cyclin E was not associated with recurrence free survival (RFS). However, when analysing the subgroup of tumours lacking a pushing growth pattern (n = 141), cyclin E was significantly associated with RFS, independent of histological grade and node status. There was no significant difference in tamoxifen response with regard to different cyclin E levels. Conclusion: The prognostic value of cyclin E in premenopausal breast cancer is limited to patients with breast carcinomas exhibiting an exclusively infiltrative growth pattern. This limitation could be explained by the presence of a small but distinct subgroup of cyclin E-high breast cancers with a pushing margin phenotype and a more favourable outcome.

  • 2.
    Burger, Gerard
    et al.
    Symbiant Pathol Expert Centre, Netherlands; University of Amsterdam, Netherlands.
    Abu-Hanna, Ameen
    University of Amsterdam, Netherlands.
    de Keizer, Nicolette
    University of Amsterdam, Netherlands.
    Cornet, Ronald
    Linköping University, Department of Biomedical Engineering, Medical Informatics. Linköping University, Faculty of Science & Engineering. University of Amsterdam, Netherlands.
    Natural language processing in pathology: a scoping review2016In: Journal of Clinical Pathology, ISSN 0021-9746, E-ISSN 1472-4146, Vol. 69, no 11, p. 949-955Article, review/survey (Refereed)
    Abstract [en]

    Background Encoded pathology data are key for medical registries and analyses, but pathology information is often expressed as free text. Objective We reviewed and assessed the use of NLP (natural language processing) for encoding pathology documents. Materials and methods Papers addressing NLP in pathology were retrieved from PubMed, Association for Computing Machinery (ACM) Digital Library and Association for Computational Linguistics (ACL) Anthology. We reviewed and summarised the study objectives; NLP methods used and their validation; software implementations; the performance on the dataset used and any reported use in practice. Results The main objectives of the 38 included papers were encoding and extraction of clinically relevant information from pathology reports. Common approaches were word/phrase matching, probabilistic machine learning and rule-based systems. Five papers (13%) compared different methods on the same dataset. Four papers did not specify the method(s) used. 18 of the 26 studies that reported F-measure, recall or precision reported values of over 0.9. Proprietary software was the most frequently mentioned category (14 studies); General Architecture for Text Engineering (GATE) was the most applied architecture overall. Practical system use was reported in four papers. Most papers used expert annotation validation. Conclusions Different methods are used in NLP research in pathology, and good performances, that is, high precision and recall, high retrieval/removal rates, are reported for all of these. Lack of validation and of shared datasets precludes performance comparison. More comparative analysis and validation are needed to provide better insight into the performance and merits of these methods.

  • 3.
    Dessauvagie, Benjamin F.
    et al.
    Leeds Teaching Hosp NHS Trust, England; Univ Leeds, England; Fiona Stanley Hosp, Australia; Univ Western Australia, Australia; Univ Western Australia, Australia.
    Lee, Andrew H. S.
    Nottingham Univ Hosp NHS Trust, England.
    Meehan, Katie
    Univ Western Australia, Australia; Univ Western Australia, Australia.
    Nijhawan, Anju
    Leeds Teaching Hosp NHS Trust, England.
    Tan, Puay Hoon
    Singapore Gen Hosp, Singapore.
    Thomas, Jeremy
    Western Gen Hosp, Scotland.
    Tie, Bibiana
    Fiona Stanley Hosp, Australia.
    Treanor, Darren
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Clinical pathology. Leeds Teaching Hosp NHS Trust, England; Univ Leeds, England.
    Umar, Seemeen
    Leeds Teaching Hosp NHS Trust, England.
    Hanby, Andrew M.
    Leeds Teaching Hosp NHS Trust, England; Univ Leeds, England.
    Millican-Slater, Rebecca
    Leeds Teaching Hosp NHS Trust, England.
    Interobserver variation in the diagnosis of fibroepithelial lesions of the breast: a multicentre audit by digital pathology2018In: Journal of Clinical Pathology, ISSN 0021-9746, E-ISSN 1472-4146, Vol. 71, no 8, p. 672-679Article in journal (Refereed)
    Abstract [en]

    Aim Fibroepithelial lesions (FELs) of the breast span a morphological continuum including lesions where distinction between cellular fibroadenoma (FA) and benign phyllodes tumour (PT) is difficult. The distinction is clinically important with FAs managed conservatively while equivocal lesions and PTs are managed with surgery. We sought to audit core biopsy diagnoses of equivocal FELs by digital pathology and to investigate whether digital point counting is useful in clarifying FEL diagnoses. Method Scanned slide images from cores and subsequent excisions of 69 equivocal FELs were examined in a multicentre audit by eight pathologists to determine the agreement and accuracy of core needle biopsy (CNB) diagnoses and by digital point counting of stromal cellularity and expansion to determine if classification could be improved. Results Interobserver variation was high on CNB with a unanimous diagnosis from all pathologists in only eight cases of FA, diagnoses of both FA and PT on the same CNB in 15 and a weak mean kappa agreement between pathologists (k=0.36). Moderate agreement was observed on CNBs among breast specialists (k=0.44) and on excision samples (k=0.49). Up to 23% of lesions confidently diagnosed as FA on CNB were PT on excision and up to 30% of lesions confidently diagnosed as PT on CNB were FA on excision. Digital point counting did not aid in the classification of FELs. Conclusion Accurate and reproducible diagnosis of equivocal FELs is difficult, particularly on CNB, resulting in poor interobserver agreement and suboptimal accuracy. Given the diagnostic difficulty, and surgical implications, equivocal FELs should be reported in consultation with experienced breast pathologists as a small number of benign FAs can be selected out from equivocal lesions.

  • 4.
    Jirström, K
    et al.
    Division of Pathology Department of Laboratory Medicine, Lund University, Malmö University Hospital, Malmö, Sweden .
    Rydén, L
    Division of Pathology Department of Laboratory Medicine, Lund University, Malmö University Hospital, Malmö, Sweden .
    Anagnostaki, L
    Division of Pathology Department of Laboratory Medicine, Lund University, Malmö University Hospital, Malmö, Sweden .
    Nordenskjöld, Bo
    Linköping University, Department of Biomedicine and Surgery, Oncology. Linköping University, Faculty of Health Sciences.
    Stål, Olle
    Linköping University, Department of Biomedicine and Surgery, Oncology. Linköping University, Faculty of Health Sciences.
    Thorstenson, S
    Department of Pathology and Cytology, Kalmar County Hospital, Kalmar, Sweden .
    Chebil, G
    Department of Pathology, Helsingborg Hospital, Helsingborg, Sweden.
    Jönsson, P-E
    Department of Surgery, Helsingborg Hospital.
    Fernö, M
    Department of Oncology, Lund University Hospital, Lund, Sweden.
    Landberg, G
    Division of Pathology Department of Laboratory Medicine, Lund University, Malmö University Hospital, Malmö, Sweden .
    Pathology parameters and adjuvant tamoxifen response in a randomised premenopausal breast cancer trial2005In: Journal of Clinical Pathology, ISSN 0021-9746, E-ISSN 1472-4146, Vol. 58, no 11, p. 1135-1142Article in journal (Refereed)
    Abstract [en]

    Background: Subgroups of breast cancer that have an impaired response to endocrine treatment, despite hormone receptor positivity, are still poorly defined. Breast cancer can be subdivided according to standard pathological parameters including histological type, grade, and assessment of proliferation. These parameters are the net result of combinations of genetic alterations effecting tumour behaviour and could potentially reflect subtypes that respond differently to endocrine treatment.

    Aims: To investigate the usefulness of these parameters as predictors of the response to tamoxifen in premenopausal women with breast cancer.

    Materials/methods: Clinically established pathological parameters were assessed and related to the tamoxifen response in 500 available tumour specimens from 564 premenopausal patients with breast cancer randomised to either two years of tamoxifen or no treatment with 14 years of follow up. Proliferation was further evaluated by immunohistochemical Ki-67 expression.

    Results: Oestrogen receptor positive ductal carcinomas responded as expected to tamoxifen, whereas the difference in recurrence free survival between control and tamoxifen treated patients was less apparent in the relatively few lobular carcinomas. For histological grade, there was no obvious difference in treatment response between the groups. The relation between proliferation and tamoxifen response seemed to be more complex, with a clear response in tumours with high and low proliferation, whereas tumours with intermediate proliferation defined by Ki-67 responded more poorly.

    Conclusions: Clinically established pathology parameters seem to mirror the endocrine treatment response and could potentially be valuable in future treatment decisions for patients with breast cancer.

  • 5.
    Jones, A Wayne
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Clinical Chemistry.
    Holmgren, P
    Uncertainty in estimating blood ethanol concentrations by analysis of vitreous humour2001In: Journal of Clinical Pathology, ISSN 0021-9746, E-ISSN 1472-4146, Vol. 54, no 9, p. 699-702Article in journal (Refereed)
    Abstract [en]

    Aims - To determine the concentrations of ethanol in femoral venous blood (FVB) and vitreous humour (VH) obtained during forensic necropsies. The ratios of ethanol concentrations in VH and FVB, the reference interval, and the associated confidence limits were calculated to provide information about the uncertainty in estimating FVB ethanol concentrations indirectly from that measured in VH. Methods - Ethanol concentrations were determined in specimens of FVB and VH obtained from 706 forensic necropsies. The specimens were analysed in duplicate by headspace gas chromatography (HS-GC), with a precision (coefficient of variation) of 1.5% at a mean ethanol concentration of 500 mg/litre. The limit of detection of ethanol in body fluids by HS-GC in routine casework was 100 mg/litre. Results - In 34 instances, ethanol was present in VH at a mean concentration of 154 mg/litre, whereas the FVB ethanol concentration was reported as negative (< 100 mg/litre). These cases were excluded from the statistical analysis. The concentration of ethanol in FVB was higher than in VH in 93 instances, with a mean difference of 160 mg/litre (range 0 to 900). The mean concentration of ethanol in FVB (n = 672) was 1340 mg/litre (SD, 990) compared with 1580 mg/litre (SD, 1190) in VH. The arithmetic mean VH/FVB ratio of ethanol was 1.19 (SD, 0.285) and the 95% range was 0.63 to 1.75. The mean and SD of the differences (log VH - log FVB) was 0.063 (SD, 0.109), which gives 95% limits of agreement (LOA) from -0.149 to 0.276. Transforming back to the original scale of measurement gives a geometric mean VH/FVB ratio of 1.16 and 95% LOA from 0.71 to 1.89. These parametric estimates are in good agreement, with a median VH/FVB ratio of 1.18 and 2.5th and 97.5th centiles of 0.63 and 1.92. Conclusions - The ethanol distribution ratios (VH/FVB) show wide variation and this calls for caution when results of analysing VH at necropsy are used to estimate the concentration in FVB. Dividing the ethanol concentration in VH by 2.0 would provide a very conservative estimate of the ethanol content in FVB, being less than the true value, with a high degree of confidence.

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